In vivo CAR T Industry Leaps Forward with Challenges Ahead

In vivo CAR T sounds like the existing class of Chimeric Antigen Receptor (CAR) T-cell therapies used to provide often individualized treatment for cancer. But they’re a new and emerging class of therapeutics with their own challenges and opportunities for manufacturers.

That’s according to Mo Heidaran, PhD, chief scientist at Cellx, who is due to give a talk at the upcoming Bioprocessing Summit in Boston.

“Whether something is a cell or gene therapy, from a regulatory perspective, depends on [the nature of] the product that’s administered to the patient,” Heidaran explains.

“And, in the United States, in vivo CAR Ts are gene therapy products and not cell therapies as some people talk about them.”

The better-known CAR T products are ex vivo, delivered via modification of patient cells, he explains. Whereas this emerging class of therapies involves delivery of a genetically engineered virus or lipid nanoparticle (LNP) that, in some cases, is stably integrated into the patient genome.

According to Heidaran, the risk of integration is higher when viruses are used.

“My colleagues at the FDA want to make sure people understand it’s very important these products must be [designed] to be very specific to the cell type, perhaps based on data about [some of these] therapies having off-target effects,” he says.

Most in vivo CAR T-cell therapies are in very early stages, with none currently approved for patients, although Heidaran says they are increasingly under investigation by larger companies since they are scalable for a wider range of patients. Also, they are believed to be more cost-effective and have similar logistics, as they don’t require lymphodepletion, he adds.

“Essentially the value driver is that you’re pharmaceuticalizing cell and gene therapy since it’s just a vial of the virus or LNP that you can use to treat many patients—almost like a drug or pill,” he says.

Among the challenges for this emerging class is that several ex vivo CAR T-cell therapies are already approved for patients. In vivo CAR T therapies treat some of the same indications, i.e., certain cancers and autoimmune diseases, he says.

“At some point there has to be a decision made by the FDA about how these [new] therapies compare, such as [running] a study or external control as to whether they’re superior or non-inferior to the same or similar approved ex vivo CAR T,” he says.

Other challenges facing this new industry are about batch sizes for manufacturing, as the equipment and processes for treating ten patients are different from needing to treat thousands. Also, he says, in vivo CAR T therapies need to be monitored to look for off-target effects, durability of response, or an immune response by the patient.

“Overall, to develop a safety profile, we need to define what the effective dose is that people are working to, as these therapies may require repeat administration, which is not done with ex vivo-generated CAR T,” he says.

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